title: Melatonin promotes proliferation and differentiation of neural stem cells subjected to hypoxia in vitro.
abstract: Melatonin, an endogenously produced neurohormone secreted by the pineal gland, has a variety of physiological functions and neuroprotective effects. It can modulate the functions of neural stem cells (NSCs) including proliferation and differentiation in embryonic brain tissue but its effect and mechanism on the stem cells in hypoxia remains to be explored. Here, we show that melatonin stimulates proliferation of NSCs during hypoxia. Additionally, it also promoted the differentiation of NSCs into neurons. However, it did not appear to exert an obvious effect on the differentiation of astrocytes. The present results have further shown that the promotional effect of NSCs proliferation by melatonin involved the MT1 receptor and increased phosphorylation of ERK1/2. The effect of melatonin on differentiation of NSCs is linked to altered expression of differentiation-related genes. In the light of these findings, it is suggested that melatonin may be beneficial as a supplement for treatment of neonatal hypoxic-ischemic brain injury for promoting the proliferation and differentiation of NSCs.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Shi-Dou
authors.initials: SD
authors.lastname: Zhao
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Liu
authors.forename: Qiu-Huan
authors.initials: QH
authors.lastname: Yuan
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Liu
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Hao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D008550:Melatonin